Ear keloids: An innovative 3‐steps combined treatment

Abstract Introduction An excessive proliferation of fibroblasts and collagen synthesis after an injury may lead to a benign fibrous tumor, known as keloid, which does not regress spontaneously. Earlobes are a very frequent site of onset, since after a trauma (i.e., piercing) keloids may develop either on the helix and on the anterior or posterior lobe, from a few months up to several years after the injury. Objectives To report the effectiveness of a combined protocol of CO2 laser + Dye laser + a portable Blue LED Light medical device for Photobiomodulation Therapy (EmoLED®). Methods Fifty‐two patients with a total of 56 ear keloids have been treated in the same session with a single CO2 laser procedure + a pulsed Dye laser procedure with an adjunctive EmoLED® procedure for 3 up to 6 min. A monthly follow‐up has been performed with an adjunctive EmoLED® session in case of signs of inflammation. Results Among 56 treated keloids, 89.3% of them (50/56) did not recur during a follow‐up period (from 6 up to 24 months, mean 16.3 months) while six keloids recurred (6/56, 10.7%) with mild thickening of the scar, thus requiring further treatments. Conclusions Even if an excellent outcome obtained by the synergistic effect of combined laser treatments has already been described (i.e., CO2 laser + Dye Laser), the present study showed the adjuvant procedure with EmoLED® can reduce significantly the risk of keloids recurrences.


INTRODUCTION
The term keloid, originating from the Greek word χηλή (chele, crab's claw), is used to describe the lateral growth of excessive proliferation of fibroblasts and collagen after a trauma, extending beyond the margins of the original skin wound, into unaffected skin. 1,2tentially, either major and minor injuries (such as piercings, trauma, surgical procedures, burns) could result into a keloid, independently of patients' age or gender, even though darker skin and range age between 10 and 30 years seem to be the most affected categories, and keloids in darker skin seem to be harder in consistency and then more difficult to treat.Each body site can see the onset of a keloid, but shoulder, chest and ears represent the most common sites.
It has been largely reported that ear piercings are the most common injuries responsible of keloids onset, with an incidence, approximately, of the 2.5%.Ear keloids can be observed either on the helix and on the anterior or posterior lobe and may develop up to several years after piercing, arising from a mature scar and do not regress spontaneously. 3,4mildly tender, single or multi-nodular, with well-circumscribed margins, pink to purple, sometimes hyperpigmented, irregular, fixed, sometimes pedunculated, with a shiny surface, and sometimes visible telangiectasia is the typical manifestation of keloids. 3,4They are mainly asymptomatic, but pruritus, pain (from mild to moderate-severe) and hyperesthesia have been reported so far.
Psychological and functional aspects have also to be evaluated: keloids can be disfiguring and, if occurring near a flexor or extensor joint, can reduce patients' motility, due to the expanding far beyond the site of initiation and encompassing entire anatomic areas.[3][4] Clinical appearance along with a history of a preceding trauma or surgery represent the most relevant clues to achieve the correct diagnosis.Differential diagnoses mainly include hypertrophic scars, due to the similar look, but a hypertrophic scar usually follows the wound's shape, and more frequently occurs on shoulders, neck, pre-sternum, knees, and ankles.[3][4][5] Among the past decades, many treatments have been proposed to approach keloids, with different degrees of reported success and different percentages of recurrences.

OBJECTIVES
We herein report four centers experience on keloids combined treatment with three different devices performed in the same session: CO2 laser for removing keloids, Dye laser to reduce the vascularization, blue light (EmoLED®) 3-6 min (depending on keloids' size) to improve and speed up the healing process.

METHODS
A multi-center study, combining the results of the aforementioned procedure, was performed from four private dermatological services (Skin Centers in L'Aquila, Avezzano, Pescara and Catania, Italy) on 52 patients aged from 11-to 78-year-old (mean 40-year-old), came in consultation for earlobe and helix keloids treatment; patients were treated with the following protocol: in the same session, CO2 laser + Pulsed Dye Laser + EmoLED® were performed on the keloid.The follow-up time has been between 6 months and 2 years after the last combined treatment.
Each patient signed an informed consent before starting treatment and the keloid lesion presented has been classified based on modified Chang-Park classification. 6 the first clinical visit, by using two different 3D digital cameras (Vectra H2, Canfield, USA and Lifeviz mini, Quantificare, France) and a smartphone for 2D images (Samsung S9), we recorded threedimensional (3D) and 2D pictures from each patient and also dermoscopic digital images of all lesions were taken by using a HEINE In all cases, patients applied a pressure earring for two weeks after combined treatment.
All patients were followed up for at least 6 months up to 2 years as follows: the first visit was scheduled one week after the combined treatment performed and then monthly.All patients were examined both clinically and with dermoscopy at each follow-up visit and clinical images were saved in our database for comparison.Inflammation itself is one of the triggers of fibroblast proliferation and therefore responsible for recurrences in keloids, thus we decided to apply EmoLED® at every follow-up visit for at least 3 min, to better exploit its modulatory effect on inflammation with the aim to prevent any recurrences.In selected cases, a further pulsed Dye laser session have been required, when dermoscopy had highlighted any sign of neo-angiogenesis.

F I G U R E 4
Type IV: A buried keloid of the helix in a 45-year-old woman.

DISCUSSION
A gold standard treatment for keloids is yet to be discovered, since the complex pathophysiologic mechanism which causes keloids is not fully understood. 8,9,10Thus, treatment options still relies on considering the type of lesion (location, depth, size), patient's age, past response to treatment, aesthetic presentation, the costs/benefits of a topical (i.e., silicone gels and sheeting, pressure dressings and pressure earrings, imiquimod 5% cream) or an invasive therapy, and expected outcome and, last but not least, patient's economic conditions.[14][15][16][17] More recently, superficial radiation therapy (SRT) has been tested [22][23] Among non-ablative lasers, pulsed-dye laser (PDL, wavelength: 585-595 nm) seems to produce a direct effect on collagen, causing keloid fibroblast functional modification, and by targeting hemoglobin chromophore, PDL coagulates the microvasculature in the capillary and reticular dermis, thus leading to hypoxemia that may alter the local collagen production.
However, PDL has an approximate 1.2 mm depth of penetration, thus keloids thicker than 1 cm may be reached mild results.In the aim to treat thicker lesions, a combination of PDL therapy plus F I G U R E 5 Type V: A 3.7 cm in-diameter mixed keloid of 2.8 cm in-diameter in a 37-year-old man, after an ear piercing.

F I G U R E 6
Before (A-left) and after (B-right) a 3-steps protocol.Follow up: 6 months (right).
intralesional corticosteroids or 5-fluorouracil injections or other lasers like the fractional CO2 laser has been investigated, but adverse effects (such as crusting, blistering, post-inflammatory hyperpigmentation and purpura) have been reported, especially in darker skin individuals. 24,25e EmoLED Medical Device, produced in Sesto Fiorentino (Florence, Italy), uses LEDs, non-coherent light sources, that emit blue light at 400−430 nm, as already described in the literature. 26,27It has a power density of 120 mW/cm 2 and an energy density estimated in 7.2 J/cm 2 .The emitted continuous radiation is made uniform over the entire area by the optical system of the device.The therapeutic the lighting industry, including biomedical applications of light, saw its onset in the 1990s.
7][28][29][30] Other authors considered that it is F I G U R E 1 0 Before (A-left) and after 6 months (B-right) our protocol.
possible that blue light is absorbed by mitochondrial chromophores in the same way as red/infrared light, but also that can be several other distinct chromophores. 31The B.L.U.R. study reported the successful and effective outcomes obtained by using blue light photobiomodulation with EmoLED® in addition to the standard of care compared to standard of care alone: at week 10, the wounds treated with additional EmoLED® showed a smaller residual wound area compared to the lesions treated with the standard of care alone, especially for venous leg ulcers, thus suggesting an important role of blue light in promoting re-epithelialization of chronic wounds of lower limbs. 32rthermore, Marchelli et al. studied the effect of blue light in patients affected by chronic wounds of different etiologies that did not respond to standard treatments.Of the 19 ulcers evaluated (venous, ischemic, post-traumatic, vasculitic), 84% responded to the treatment during the period of observation, and the treatment showed a good safety profile. 33,34 considering its mechanism, we decided to apply EmoLED® technology as a third step in our keloid-treatment protocol, in the aim to improve wound healing after the lasers injury and to try to inhibit recurrences.In our experience, the combination of two or three Laser led to a 14.6% of keloids recurrence which was already an interesting result. 35,36 the present study, the adjunctive final session with EmoLED®, by targeting directly the inflammation molecules thus reducing the fibroblast proliferation, led to only a 10.7% of keloid recurrence, which is to be considered a significant result in this field.

CONCLUSIONS
The effectiveness reported by three-steps laser-blue light protocol is based on the concept of using different phototherapies in the aim to potentially target different keloids pathways.Our results confirmed the disappearance of keloids in the absence of recurrences in the 89.3% of cases, even over the long term, and even if these lesions have been previously treated with traditional surgery.Our results are thus promising, although the small sample of enrolled population represents a study limit, so larger investigations are needed to further demonstrate the potential clinical application of this three-steps combined protocol in treating ear keloids and in avoiding recurrences.
Laser devices have been deeply investigated in recent years and have been tested on several different dermatological conditions.Due to the large spectrum of different target, each type of laser device could reach and interact different epidermal and dermal structures, thus leading to a wide range of therapeutic options.Piccolo et al. have recently published a comparative study on combined lasers treatment for ear keloids, showing how the combination of CO2 laser + Dye laser followed by a pneumatic injection without needle of drugs (a solution of 1 mL of Triamcinolone, 3 mL of polyribonucleotides and 2 mL of sodium chloride) Our results confirmed the disappearance of the lesion in the absence of recurrences in the 88% of cases, even over the long term, and even if these lesions have been treated with traditional surgery in the meantime.
Cube hardware (connected to I-Phone XS equipped with HEINE Cube software, Monaco, Germany).The same types of pictures acquisition have been performed at each follow-up control.Each picture has been stored in a digital database.The use of dermoscopy has proved to be very useful in the treatment of keloids (as well as hypertrophic scars and other lesions), due to its capability of highlights the presence of possible pigmentation and neo-vascularization, thus helping physicians in the therapeutic choice: by identifying the targets to hit, lasers can be properly chosen.7,8All 52 patients enrolled have been treated in the same session with a single CO2 laser (Smartxide Touch, DEKA M.E.L.A., Calenzano, Italy) procedure, by shaving keloid (Power 4 W and frequency 80 Hz in ultra-pulsed mode) followed by a single Pulsed Dye Laser (VasQ, DEKA M.E.L.A., Calenzano, Italy) procedure (fluence: 11J/cm 2 ; single pulse, pulse duration 1.5 ms, PDL spot 5-7 mm) on each lesion.If the lesion was greater than 2,5 cm in-diameter, an adjunctive Pulsed Dye Laser session has been performed 40 days earlier (fluency: 14J/cm 2 ; single pulse, pulse duration 3 ms, PDL spot 5 to 7 mm), with the aim to reduce the blood vessels' number and to reduce the release of pro-inflammatory cytokines (such as VEGF), thus leading the lesion to become smaller, softer and less vascularized.A topic antibiotic and silver sulfadiazine cream were prescribed to each patient as home care.All patients underwent to a third and final treatment with EmoLED®: it uses LED sources that emit visible light with wavelengths in the blue region (400-430 nm) and is equipped with a sophisticated optical system that allows for a homogeneous and controlled emission.Each single application is carried out on a circular area with a diameter of 50 mm.In the case of larger lesions, successive applications on adjacent areas should be performed for complete treatment until the entire area of the lesion is covered.To facilitate the operator, the device is equipped with software for the automatic calculation of the number of applications necessary for the treatment of the entire lesion; it is sufficient for the operator to enter the dimensions of the wound using the touch screen with an intuitive interface with which the device is equipped.The device is not in contact with the treated area: a distance of 4 cm from the wound bed must be maintained during treatment and the device is programmed to emit light only if positioned at the correct distance from the target area.An optoelectronic sensor and a distance indicator visible on the touch screen during execution help the operator to identify and maintain correct positioning.The treatment is well tolerated by the patients.

F I G U R E 1
Type I: A 1.3 cm in-diameter pedunculated keloid of the helix, in a 18-year-old woman.F I G U R E 2 Type II: A sessile, 2 cm in-diameter keloid with single nodular pattern in a 21-year-old man arose after an ear piercing.between the fourth and the eleventh month of follow up.These 6 recurrences were mainly represented by a mild thickening and mild grade of neoangiogenesis (evidenced by dermoscopy) of the scar and have been immediately re-treated with a Dye laser session.Up to now, all those six recurrences did not relapse anymore.F I G U R E 3 Type III: A sessile with multi nodular pattern keloid in a 58-year-old man, arose after surgery.
cancers and recurrent keloids.As a matter of fact, in 2019 Nestor MS et al. reported on postsurgical treatment of keloid excision suture lines with SRT with a significant reduction of keloid recurrence rates with no evidence that the exposed surrounding healthy skin subsequently develop skin cancer.Thus, SRT has now (2023) been introduced as a therapeutical option in treating recurrent keloid scars that are resistant to other therapies with three postsurgical fractions, according to the Zemtsov-Cognetta criteria. 18-19Many lasers/devices types have been recently studied and applied to keloids treatments in recent years: ablative lasers such as yttrium, aluminum, and garnet (Er:YAG) laser and 10,600-nm carbon dioxide (CO2), whose target chromophore in skin is water, and therefore can provoke local tissue destruction; non-ablative lasers such as pulsed-dye laser (PDL), the 1064-nm neodymium-doped: yttrium, aluminum and garnet (Nd:YAG) laser, and the 532-nm neodymiumdoped:vanadate (Nd:Van) laser; non-coherent light sources such as intense pulsed light therapy (IPL), light-emitting diode (LED) phototherapy, and photodynamic therapy (PDT). 20CO2 laser excision without adjunctive therapy has a high rate of recurrence (similar to simple surgical excision), ranging from 74% to 100% in 1 year.An adjunctive intralesional steroid therapy and/or cyanoacrylate glue have been shown to improve CO2 laser keloid excision outcomes.Multiple ablative CO2 treatments are necessary for longer-lasting scar and have shown an improvement of keloid pigmentation, pliability, and scar bulk at six months after the last treatment.Scrimali et al.

F I G U R E 7
Before (A-left) and after (B-right) our three steps protocol.Follow up: after 6 months (C) and 1 year (D).effect of light occurs thanks to the presence in the tissues of endogenous molecules capable of absorbing it: the energy conveyed by the light beam is absorbed by chromophores naturally present in the tissues, and used to promote chemical reactions or produce changes conformational in some biomolecules.This process results in beneficial therapeutic effects such as reduction of pain and inflammation, immunomodulation and induction of wound healing and tissue regeneration.This therapeutic process was defined "Photobiomodulation" in 2014 by the North American Association for Laser Therapy and the World Association for Laser Therapy, in a joint conference.First developed in 1960s, the introduction of high-efficiency LEDs revolutionized F I G U R E 8 Before (A-left) and after (B-right) our protocol.Follow up: 3 years (C).F I G U R E 9 Before (A-left) and after 3 months (B-right).
types of laser therapy by considering their different target, interesting results have been achieved.As a matter of fact, we have already proposed another combined treatment for earlobe keloids where we reported a remarkable outcome: the combination of CO2 and Dye